We have shown that extracts of various cultured human and murine tumor cell lines contain lectin-like activity. The ability of exogenous glycoproteins to enhance cell aggregation indicated that some of the lectin activity is present at the cell surface. Since endogenous lectins are excellent candidates for mediating cognitive intercellular adhesion by binding with carbohydrate-containing surface membrane components on adjacent cells or in the extracellular matrix, we raised the hypothesis that lectins present on the surface of metastatic tumor cells that reach the circulation can promote cell aggregation (embolization) and a subsequent arrest in certain organs. The objective of this project is to determine what role do tumor cell-surface lectins play in metastasis. Two established model systems of experimental metastasis will be used. They consist of cell variants of a murine melanoma and a murine fibrosarcoma which exhibit different metastatic potentials after injection into the tail vein of syngeneic mice. Lectins will be isolated from tumor cell extracts by affinity chromatography using immobilized galactoside. The physiochemical properties of the lectins will be studied and their amounts in different tumor cells will be determined by radioimmunoassay using monoclonal anti-lectin antibodies. These antibodies will be used to probe the function of endogenous lectins by pretreating tumor cells with the antibody followed by analysis of the effect of such a treatment on cell-cell aggregation and adhesion in vitro, as well as on organ implantation and colonization in vivo. The anti-lectin antibodies will also be used for immunoselection of cell variants which express low levels of lectin on their surface and their metastatic potential will be compared with that of lectin-expressing cells. These studies are expected to allow a critical evaluation of the role of tumor cell surface lectins in metastasis. (A)